A promoter region of a gene is one which controls the expression of the gene. The myostatin gene was isolated and sequenced and the sequence published (McPherron A C; Lawler A M and Lee S J; Nature 387, 1 May 1997; WO94/21681). However the sequence of the promoter region of this gene has not been isolated, sequenced or published to date.
Myostatin, also known as growth and differentiating factor-8 (GDF-8), is structurally related to the transforming growth factor β (TGF-β) superfamily (McPherron et al 1997). The myostatin gene has been shown to inhibit muscle growth and initial research concluded that targeted disruption of the myostatin gene in mice leads to a twofold increase in muscle mass (McPherron et al 1997) indicating that the myostatin gene is a negative regulator of muscle mass.
Three of the present inventors (Kambadur, Sharma and Bass) have identified a mutation of the myostatin gene in “double muscled” Belgian Blue cattle comprising an 11 bp deletion (Kambadur et al 1997). This mutation negates the effect of myostatin and leads to a 30% or 40% increase in muscle mass.
The inventors have further observed two Belgian Blue sire lines which possess the same Belgian blue allele, i.e. the 11 bp deletion, but which is being expressed in very small amounts. On a northern blot, two bands were seen suggesting that in these animals there is a double mutation of the myostatin gene, ie hypomorphic alleles. This strongly suggests that a failure in the upstream regions of the myostatin gene have resulted in a lack of expression of myostatin and as a consequence increased muscle growth.